Association of muscular strength and targeted proteomics involved in brain health in children with overweight/obesity

Muscular strength has been positively associated with better brain health indicators during childhood obesity. However, the molecular mechanisms underlying the positive impact of muscular strength in brain health are poorly understood. We aimed to study the association of muscular strength with neurology-related circulating proteins in plasma in children with overweight/obesity and to explore the role of cardiorespiratory fitness (CRF) as a confounder. The participants were 86 Caucasian children (10.1 ± 1.1 years old; 41% girls) from the ActiveBrains project. Muscular strength was measured by field and laboratory tests. CRF was assessed with an incremental treadmill test. Olink's technology was used to quantify 92 neurology-related proteins in plasma. Protein–protein interactions were computed using the STRING website. Muscular strength was positively associated with 12 proteins (BetaNGF, CDH6, CLEC10A, CLM1, FcRL2, HAGH, IL12, LAIR2, MSR1, SCARB2, SMOC2, and TNFRSF12A), and negatively associated with 12 proteins (CLEC1B, CTSC, CTSS, gal-8, GCP5, NAAA, NrCAM, NTRK2, PLXNB3, RSPO1, sFRP3, and THY1). After adjustment for CRF, muscular strength was positively associated with eight proteins (BetaNGF, CDH6, CLEC10A, FcRL2, LAIR2, MSR1, SCARB2, and TNFRSF12A) and negatively associated with two proteins (gal-8 and NrCAM). After applying FDR correction, only CLEC10A remained statistically significant. In conclusion, muscular strength was associated with blood circulating proteins involved in several biological processes, particularly anti-inflammatory response, lipid metabolism, beta amyloid clearance, and neuronal action potential propagation. More powered studies are warranted in pediatric populations to contrast or confirm our findings

Active Gains in brain Using Exercise During Aging (AGUEDA): protocol for a randomized controlled trial

Alzheimer’s disease is currently the leading cause of dementia and one of the most expensive, lethal and severe diseases worldwide. Age-related decline in executive function is widespread and plays a key role in subsequent dementia risk. Physical exercise has been proposed as one of the leading non-pharmaceutical approaches to improve executive function and ameliorate cognitive decline. This single-site, two-arm, single-blinded, randomized controlled trial (RCT) will include 90 cognitively normal older adults, aged 65–80 years old. Participants will be randomized to a 24-week resistance exercise program (3 sessions/week, 60 min/session, n = 45), or a wait-list control group (n = 45) which will be asked to maintain their usual lifestyle. All study outcomes will be assessed at baseline and at 24-weeks after the exercise program, with a subset of selected outcomes assessed at 12-weeks. The primary outcome will be indicated by the change in an executive function composite score assessed with a comprehensive neuropsychological battery and the National Institutes of Health Toolbox Cognition Battery. Secondary outcomes will include changes in brain structure and function and amyloid deposition, other cognitive outcomes, and changes in molecular biomarkers assessed in blood, saliva, and fecal samples, physical function, muscular strength, body composition, mental health, and psychosocial parameters. We expect that the resistance exercise program will have positive effects on executive function and related brain structure and function, and will help to understand the molecular, structural, functional, and psychosocial mechanisms involvedRTI2018-095284-J-100 funded by MCIN/AEI/10.13039/501100011033/ and “ERDF A way of making Europe”RYC2019-027287-I funded by MCIN/AEI/10.13039/501100011033/ and “ESF Investing in your future”“Margarita Salas” grant from the Spanish Ministry Universities. Plan Andaluz de Investigación (PAIDI) (Convocatoria 2020, Ref: P20_00124) 2021–2022.Ministerio de Economía y Competitividad–Proyectos I + D + I RETOS (Convocatoria 2020, Ref: PID2020-120249RB-I00).EXERNET Research Network on Exercise and Health (DEP2005- 00046/ACTI; 09/UPB/19; 45/UPB/20; 27/UPB/21).University of Granada “Proyectos de investigación precompetitivos para jóvenes investigadores” (Convocatoria 2021, Ref: PPJIA2021-39)

Active Gains in brain Using Exercise During Aging (AGUEDA): protocol for a randomized controlled trial

Alzheimer’s disease is currently the leading cause of dementia and one of the most expensive, lethal and severe diseases worldwide. Age-related decline in executive function is widespread and plays a key role in subsequent dementia risk. Physical exercise has been proposed as one of the leading non-pharmaceutical approaches to improve executive function and ameliorate cognitive decline. This single-site, two-arm, single-blinded, randomized controlled trial (RCT) will include 90 cognitively normal older adults, aged 65–80 years old. Participants will be randomized to a 24-week resistance exercise program (3 sessions/week, 60 min/session, n = 45), or a wait-list control group (n = 45) which will be asked to maintain their usual lifestyle. All study outcomes will be assessed at baseline and at 24-weeks after the exercise program, with a subset of selected outcomes assessed at 12-weeks. The primary outcome will be indicated by the change in an executive function composite score assessed with a comprehensive neuropsychological battery and the National Institutes of Health Toolbox Cognition Battery. Secondary outcomes will include changes in brain structure and function and amyloid deposition, other cognitive outcomes, and changes in molecular biomarkers assessed in blood, saliva, and fecal samples, physical function, muscular strength, body composition, mental health, and psychosocial parameters. We expect that the resistance exercise program will have positive effects on executive function and related brain structure and function, and will help to understand the molecular, structural, functional, and psychosocial mechanisms involved

Prosomeric Hypothalamic Distribution of Tyrosine Hydroxylase Positive Cells in Adolescent Rats

Most of the studies on neurochemical mapping, connectivity, and physiology in the hypothalamic region were carried out in rats and under the columnar morphologic paradigm. According to the columnar model, the entire hypothalamic region lies ventrally within the diencephalon, which includes preoptic, anterior, tuberal, and mamillary anteroposterior regions, and sometimes identifying dorsal, intermediate, and ventral hypothalamic partitions. This model is weak in providing little or no experimentally corroborated causal explanation of such subdivisions. In contrast, the modern prosomeric model uses different axial assumptions based on the parallel courses of the brain floor, alar-basal boundary, and brain roof (all causally explained). This model also postulates that the hypothalamus and telencephalon jointly form the secondary prosencephalon, separately from and rostral to the diencephalon proper. The hypothalamus is divided into two neuromeric (transverse) parts called peduncular and terminal hypothalamus (PHy and THy). The classic anteroposterior (AP) divisions of the columnar hypothalamus are rather seen as dorsoventral subdivisions of the hypothalamic alar and basal plates. In this study, we offered a prosomeric immunohistochemical mapping in the rat of hypothalamic cells expressing tyrosine hydroxylase (TH), which is the enzyme that catalyzes the conversion of L-tyrosine to levodopa (L-DOPA) and a precursor of dopamine. This mapping was also combined with markers for diverse hypothalamic nuclei [agouti-related peptide (Agrp), arginine vasopressin (Avp), cocaine and amphetamine-regulated transcript (Cart), corticotropin releasing Hormone (Crh), melanin concentrating hormone (Mch), neuropeptide Y (Npy), oxytocin/neurophysin I (Oxt), proopiomelanocortin (Pomc), somatostatin (Sst), tyrosine hidroxilase (Th), and thyrotropin releasing hormone (Trh)]. TH-positive cells are particularly abundant within the periventricular stratum of the paraventricular and subparaventricular alar domains. In the tuberal region, most labeled cells are found in the acroterminal arcuate nucleus and in the terminal periventricular stratum. The dorsal retrotuberal region (PHy) contains the A13 cell group of TH-positive cells. In addition, some TH cells appear in the perimamillary and retromamillary regions. The prosomeric model proved useful for determining the precise location of TH-positive cells relative to possible origins of morphogenetic signals, thus aiding potential causal explanation of position-related specification of this hypothalamic cell type.Fil: Bilbao, María Guillermina. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; ArgentinaFil: Garrigos, Daniel. Universidad de Murcia; EspañaFil: Martinez Morga, Marta. Universidad de Murcia; EspañaFil: Toval, Angel. Universidad de Murcia; EspañaFil: Kutsenko, Yevheniy. Universidad de Murcia; EspañaFil: Bautista, Rosario. Universidad de Murcia; EspañaFil: Barreda, Alberto. Universidad de Murcia; EspañaFil: Ribeiro Do Couto, Bruno. Universidad de Murcia; EspañaFil: Puelles, Luis. Universidad de Murcia; EspañaFil: Ferran, José Luis. Universidad de Murcia; Españ

Dopaminergic Modulation of Forced Running Performance in Adolescent Rats: Role of Striatal D1 and Extra-striatal D2 Dopamine Receptors

Improving exercise capacity during adolescence impacts positively on cognitive and motor functions. However, the neural mechanisms contributing to enhance physical performance during this sensitive period remain poorly understood. Such knowledge could help to optimize exercise programs and promote a healthy physical and cognitive development in youth athletes. The central dopamine system is of great interest because of its role in regulating motor behavior through the activation of D1 and D2 receptors. Thus, the aim of the present study is to determine whether D1 or D2 receptor signaling contributes to modulate the exercise capacity during adolescence and if this modulation takes place through the striatum. To test this, we used a rodent model of forced running wheel that we implemented recently to assess the exercise capacity. Briefly, rats were exposed to an 8-day period of habituation in the running wheel before assessing their locomotor performance in response to an incremental exercise test, in which the speed was gradually increased until exhaustion. We found that systemic administration of D1-like (SCH23390) and/or D2-like (raclopride) receptor antagonists prior to the incremental test reduced the duration of forced running in a dose-dependent manner. Similarly, locomotor activity in the open field was decreased by the dopamine antagonists. Interestingly, this was not the case following intrastriatal infusion of an effective dose of SCH23390, which decreased motor performance during the incremental test without disrupting the behavioral response in the open field. Surprisingly, intrastriatal delivery of raclopride failed to impact the duration of forced running. Altogether, these results indicate that the level of locomotor response to incremental loads of forced running in adolescent rats is dopamine dependent and mechanistically linked to the activation of striatal D1 and extra-striatal D2 receptors

Hypothalamic Crh/Avp, plasmatic glucose and lactate remain unchanged during habituation to forced exercise

It has been demonstrated that physical activity contributes to a healthier life. However, there is a knowledge gap regarding the neural mechanisms producing these effects. One of the keystones to deal with this problem is to use training programs with equal loads of physical activity. However, irregular motor and stress responses have been found in murine exercise models. Habituation to forced exercise facilitates a complete response to a training program in all rodents, reaching the same load of physical activity among animals. Here, it was evaluated if glucose and lactate – which are stress biomarkers – are increased during the habituation to exercise. Sprague-Dawley rats received an 8-days habituation protocol with progressive increments of time and speed of running. Then, experimental and control (non-habituated) rats were subjected to an incremental test. Blood samples were obtained to determine plasmatic glucose and lactate levels before, immediately after and 30 min after each session of training. Crh and Avp mRNA expression was determined by two-step qPCR. Our results revealed that glucose and lactate levels are not increased during the habituation period and tend to decrease toward the end of the protocol. Also, Crh and Avp were not chronically activated by the habituation program. Lactate and glucose, determined after the incremental test, were higher in control rats without previous contact with the wheel, compared with habituated and wheel control rats. These results suggest that the implementation of an adaptive phase prior to forced exercise programs might avoid non-specific stress responses

Active Gains in brain Using Exercise During Aging (AGUEDA) : protocol for a randomized controlled trial

Alzheimer’s disease is currently the leading cause of dementia and one of the most expensive, lethal and severe diseases worldwide. Age-related decline in executive function is widespread and plays a key role in subsequent dementia risk. Physical exercise has been proposed as one of the leading non-pharmaceutical approaches to improve executive function and ameliorate cognitive decline. This single-site, two-arm, single-blinded, randomized controlled trial (RCT) will include 90 cognitively normal older adults, aged 65–80 years old. Participants will be randomized to a 24-week resistance exercise program (3 sessions/week, 60 min/session, n = 45), or a wait-list control group (n = 45) which will be asked to maintain their usual lifestyle. All study outcomes will be assessed at baseline and at 24-weeks after the exercise program, with a subset of selected outcomes assessed at 12-weeks. The primary outcome will be indicated by the change in an executive function composite score assessed with a comprehensive neuropsychological battery and the National Institutes of Health Toolbox Cognition Battery. Secondary outcomes will include changes in brain structure and function and amyloid deposition, other cognitive outcomes, and changes in molecular biomarkers assessed in blood, saliva, and fecal samples, physical function, muscular strength, body composition, mental health, and psychosocial parameters. We expect that the resistance exercise program will have positive effects on executive function and related brain structure and function, and will help to understand the molecular, structural, functional, and psychosocial mechanisms involved.peerReviewe